This proposal has two main objectives: 1. to create a research laboratory on drug abuse; 2. to expand ongoing research on substance abuse. Objective 1 can be achieved by the infrastructure proposed in the proposal which allows acquiring equipment and creating an environment conductive to drug related research. This will attract students to pursue research careers in pharmacology. Included in the infrastructure are seminars, consultants and experts on drug abuse research who will encourage students and faculty to extend their interest in these areas. To meet the second objective, 3 projects have been included. Project 1 proposes to determine the level as well as monitor the time course of changes in the level of monoamines and acetylcholine following acute and chronic doses of cocaine. The purpose is to investigate how cocaine affects individual neurotransmitter at various brain regions. Project Ii proposes to study the acute and chronic effects of variable doses of cocaine on behavioral activity, eg., locomotor activity and stereotypies; and follow the pattern of behavioral changes during he course of cocaine administration. Receptor affinity and density at cocaine binding sites in brain regions will be measured. Data obtained in this project should delineate the process of sensitization and/or tolerance observed with cocaine use. Since project I and II will be conducted in parallel, combined data should disclose the relationship, if any, between altered behavioral and neurochemical levels. Project III will be engaged in the development of compounds to compensate or block the undesirable effects of CNS stimulants, substance of abuse. Project III will design and synthesize new compounds based on structure activity relationships which will be tested by methodology in projects I and II to evaluate their therapeutic potential as antagonistic compounds which are not currently available. Both portions of the proposal have a central goal. The infrastructure portion of the proposal will increase enrollment of minority students and faculty to pursue careers in drug abuse related research. It is hoped that this proposal will significantly contribute to the mostly needed research areas of drug abuse.